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Human deficiencies of fucosylation and sialylation affecting selectin ligands

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Abstract

Selectins are carbohydrate-binding adhesion molecules that are required for leukocyte trafficking to secondary lymphoid organs and to sites of infection. They interact with fucosylated and sialylated ligands bearing sialyl-Lewis X as a minimal carbohydrate structure. With this in mind, it should be expected that individuals with deficient fucosylation or sialylation show immunodeficiency. However, as this review shows, the picture appears to be more complex and more interesting. Although there are only few patients with such glycosylation defects, they have turned out to be very instructive for our understanding of the functions of fucosylation and sialylation in immunity, development and hemostasis.

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References

  1. Gallatin WM, Weissman IL, Butcher EC (1983) A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature 304:30–34

    Article  PubMed  CAS  Google Scholar 

  2. Huang MC, Laskowska A, Vestweber D, Wild MK (2002) The alpha (1,3)-fucosyltransferase Fuc-TIV, but not Fuc-TVII, generates sialyl Lewis X-like epitopes preferentially on glycolipids. J Biol Chem 277:47786–47795

    Article  PubMed  CAS  Google Scholar 

  3. Luo Y, Haltiwanger RS (2005) O-fucosylation of notch occurs in the endoplasmic reticulum. J Biol Chem 280:11289–11294

    Article  PubMed  CAS  Google Scholar 

  4. Sasaki K, Watanabe E, Kawashima K, Sekine S, Dohi T, Oshima M, Hanai N, Nishi T, Hasegawa M (1993) Expression cloning of a novel Gal beta (1-3/1-4) GlcNAc alpha 2,3-sialyltransferase using lectin resistance selection. J Biol Chem 268:22782–22787

    PubMed  CAS  Google Scholar 

  5. Okajima T, Fukumoto S, Miyazaki H, Ishida H, Kiso M, Furukawa K, Urano T (1999) Molecular cloning of a novel alpha2,3-sialyltransferase (ST3Gal VI) that sialylates type II lactosamine structures on glycoproteins and glycolipids. J Biol Chem 274:11479–11486

    Article  PubMed  CAS  Google Scholar 

  6. Ellies LG, Ditto D, Levy GG, Wahrenbrock M, Ginsburg D, Varki A, Le DT, Marth JD (2002) Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands. Proc Natl Acad Sci U S A 99:10042–10047

    Article  PubMed  CAS  Google Scholar 

  7. Ellies LG, Sperandio M, Underhill GH, Yousif J, Smith M, Priatel JJ, Kansas GS, Ley K, Marth JD (2002) Sialyltransferase specificity in selectin ligand formation. Blood 100:3618–3625

    Article  PubMed  CAS  Google Scholar 

  8. Maly P, Thall A, Petryniak B, Rogers CE, Smith PL, Marks RM, Kelly RJ, Gersten KM, Cheng G, Saunders TL, Camper SA, Camphausen RT, Sullivan FX, Isogai Y, Hindsgaul O, von Andrian UH, Lowe JB (1996) The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis. Cell 86:643–653

    Article  PubMed  CAS  Google Scholar 

  9. Homeister JW, Thall AD, Petryniak B, Maly P, Rogers CE, Smith PL, Kelly RJ, Gersten KM, Askari SW, Cheng G, Smithson G, Marks RM, Misra AK, Hindsgaul O, von Andrian UH, Lowe JB (2001) The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing. Immunity 15:115–126

    Article  PubMed  CAS  Google Scholar 

  10. Anderson DC, Springer TA (1987) Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med 38:175–194

    Article  PubMed  CAS  Google Scholar 

  11. Kuijpers TW, Van Lier RA, Hamann D, de Boer M, Thung LY, Weening RS, Verhoeven AJ, Roos D (1997) Leukocyte adhesion deficiency type 1 (LAD-1)/variant. A novel immunodeficiency syndrome characterized by dysfunctional beta2 integrins. J Clin Invest 100:1725–1733

    Article  PubMed  CAS  Google Scholar 

  12. Hogg N, Stewart MP, Scarth SL, Newton R, Shaw JM, Law SK, Klein N (1999) A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest 103:97–106

    Article  PubMed  CAS  Google Scholar 

  13. Moser M, Bauer M, Schmid S, Ruppert R, Schmidt S, Sixt M, Wang HV, Sperandio M, Fassler R (2009) Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to endothelial cells. Nat Med 15:300–305

    Article  PubMed  CAS  Google Scholar 

  14. Svensson L, Howarth K, McDowall A, Patzak I, Evans R, Ussar S, Moser M, Metin A, Fried M, Tomlinson I, Hogg N (2009) Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation. Nat Med 15:306–312

    Article  PubMed  CAS  Google Scholar 

  15. Etzioni A, Frydman M, Pollack S, Avidor I, Phillips ML, Paulson JC, Gershoni-Baruch R (1992) Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med 327:1789–1792

    Article  PubMed  CAS  Google Scholar 

  16. Marquardt T, Brune T, Lühn K, Zimmer KP, Korner C, Fabritz L, van der Werft N, Vormoor J, Freeze HH, Louwen F, Biermann B, Harms E, von Figura K, Vestweber D, Koch HG (1999) Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism. J Pediatr 134:681–688

    Article  PubMed  CAS  Google Scholar 

  17. Hidalgo A, Ma S, Peired AJ, Weiss LA, Cunningham-Rundles C, Frenette PS (2003) Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene. Blood 101:1705–1712

    Article  PubMed  CAS  Google Scholar 

  18. Helmus Y, Denecke J, Yakubenia S, Robinson P, Lühn K, Watson DL, McGrogan PJ, Vestweber D, Marquardt T, Wild MK (2006) Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter. Blood 107:3959–3966

    Article  PubMed  CAS  Google Scholar 

  19. Frydman M, Etzioni A, Eidlitz-Markus T, Avidor I, Varsano I, Shechter Y, Orlin JB, Gershoni-Baruch R (1992) Rambam–Hasharon syndrome of psychomotor retardation, short stature, defective neutrophil motility, and Bombay phenotype. Am J Med Genet 44:297–302

    Article  PubMed  CAS  Google Scholar 

  20. Shechter Y, Etzioni A, Levene C, Greenwell P (1995) A Bombay individual lacking H and Le antigens but expressing normal levels of alpha-2- and alpha-4-fucosyltransferases. Transfusion 35:773–776

    Article  PubMed  CAS  Google Scholar 

  21. Lübke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Korner C (2001) Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nat Genet 28:73–76

    PubMed  Google Scholar 

  22. Lühn K, Wild MK, Eckhardt M, Gerardy-Schahn R, Vestweber D (2001) The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. Nat Genet 28:69–72

    PubMed  Google Scholar 

  23. Etzioni A, Sturla L, Antonellis A, Green ED, Gershoni-Baruch R, Berninsone PM, Hirschberg CB, Tonetti M (2002) Leukocyte adhesion deficiency (LAD) type II/carbohydrate deficient glycoprotein (CDG) IIc founder effect and genotype/phenotype correlation. Am J Med Genet 110:131–135

    Article  PubMed  Google Scholar 

  24. Price TH, Ochs HD, Gershoni-Baruch R, Harlan JM, Etzioni A (1994) In vivo neutrophil and lymphocyte function studies in a patient with leukocyte adhesion deficiency type II. Blood 84:1635–1639

    PubMed  CAS  Google Scholar 

  25. Phillips ML, Schwartz BR, Etzioni A, Bayer R, Ochs HD, Paulson JC, Harlan JM (1995) Neutrophil adhesion in leukocyte adhesion deficiency syndrome type 2. J Clin Invest 96:2898–2906

    Article  PubMed  CAS  Google Scholar 

  26. Hellbusch CC, Sperandio M, Frommhold D, Yakubenia S, Wild MK, Popovici D, Vestweber D, Grone HJ, von Figura K, Lubke T, Korner C (2007) Golgi GDP-fucose transporter-deficient mice mimic congenital disorder of glycosylation IIc/leukocyte adhesion deficiency II. J Biol Chem 282:10762–10772

    Article  PubMed  CAS  Google Scholar 

  27. Smith PL, Myers JT, Rogers CE, Zhou L, Petryniak B, Becker DJ, Homeister JW, Lowe JB (2002) Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus. J Cell Biol 158:801–815

    Article  PubMed  CAS  Google Scholar 

  28. Zhou L, Li LW, Yan Q, Petryniak B, Man Y, Su C, Shim J, Chervin S, Lowe JB (2008) Notch-dependent control of myelopoiesis is regulated by fucosylation. Blood 112:308–319

    Article  PubMed  CAS  Google Scholar 

  29. Yao D, Huang Y, Huang X, Wang W, Yan Q, Wei L, Xin W, Gerson S, Stanley P, Lowe JB, Zhou L (2011) Protein O-fucosyltransferase 1 (Pofut1) regulates lymphoid and myeloid homeostasis through modulation of Notch receptor ligand interactions. Blood 117:5652–5662

    Article  PubMed  CAS  Google Scholar 

  30. von Andrian UH, Berger EM, Ramezani L, Chambers JD, Ochs HD, Harlan JM, Paulson JC, Etzioni A, Arfors KE (1993) In vivo behavior of neutrophils from two patients with distinct inherited leukocyte adhesion deficiency syndromes. J Clin Invest 91:2893–2897

    Article  Google Scholar 

  31. Yakubenia S, Frommhold D, Scholch D, Hellbusch CC, Korner C, Petri B, Jones C, Ipe U, Bixel MG, Krempien R, Sperandio M, Wild MK (2008) Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc. Blood 112:1472–1481

    Article  PubMed  CAS  Google Scholar 

  32. Kuijpers TW, Etzioni A, Pollack S, Pals ST (1997) Antigen-specific immune responsiveness and lymphocyte recruitment in leukocyte adhesion deficiency type II. Int Immunol 9:607–613

    Article  PubMed  CAS  Google Scholar 

  33. Etzioni A, Gershoni-Baruch R, Pollack S, Shehadeh N (1998) Leukocyte adhesion deficiency type II: long-term follow-up. J Allergy Clin Immunol 102:323–324

    Article  PubMed  CAS  Google Scholar 

  34. Radtke F, Wilson A, Mancini SJ, MacDonald HR (2004) Notch regulation of lymphocyte development and function. Nat Immunol 5:247–253

    Article  PubMed  CAS  Google Scholar 

  35. Yoon K, Gaiano N (2005) Notch signaling in the mammalian central nervous system: insights from mouse mutants. Nat Neurosci 8:709–715

    Article  PubMed  CAS  Google Scholar 

  36. Okajima T, Xu A, Irvine KD (2003) Modulation of notch-ligand binding by protein O-fucosyltransferase 1 and fringe. J Biol Chem 278:42340–42345

    Article  PubMed  CAS  Google Scholar 

  37. Sasamura T, Sasaki N, Miyashita F, Nakao S, Ishikawa HO, Ito M, Kitagawa M, Harigaya K, Spana E, Bilder D, Perrimon N, Matsuno K (2003) Neurotic, a novel maternal neurogenic gene, encodes an O-fucosyltransferase that is essential for Notch–Delta interactions. Development 130:4785–4795

    Article  PubMed  CAS  Google Scholar 

  38. Shi S, Stanley P (2003) Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways. Proc Natl Acad Sci U S A 100:5234–5239

    Article  PubMed  CAS  Google Scholar 

  39. Sturla L, Rampal R, Haltiwanger RS, Fruscione F, Etzioni A, Tonetti M (2003) Differential terminal fucosylation of N-linked glycans versus protein O-fucosylation in leukocyte adhesion deficiency type II (CDG IIc). J Biol Chem 278:26727–26733

    Article  PubMed  CAS  Google Scholar 

  40. Waterhouse CC, Johnson S, Phillipson M, Zbytnuik L, Petri B, Kelly M, Lowe JB, Kubes P (2010) Secretory cell hyperplasia and defects in Notch activity in a mouse model of leukocyte adhesion deficiency type II. Gastroenterology 138(1079–1090):e1071–e1075

    Google Scholar 

  41. Wang X, Inoue S, Gu J, Miyoshi E, Noda K, Li W, Mizuno-Horikawa Y, Nakano M, Asahi M, Takahashi M, Uozumi N, Ihara S, Lee SH, Ikeda Y, Yamaguchi Y, Aze Y, Tomiyama Y, Fujii J, Suzuki K, Kondo A, Shapiro SD, Lopez-Otin C, Kuwaki T, Okabe M, Honke K, Taniguchi N (2005) Dysregulation of TGF-beta1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice. Proc Natl Acad Sci U S A 102:15791–15796

    Article  PubMed  CAS  Google Scholar 

  42. Wang X, Gu J, Ihara H, Miyoshi E, Honke K, Taniguchi N (2006) Core fucosylation regulates epidermal growth factor receptor-mediated intracellular signaling. J Biol Chem 281:2572–2577

    Article  PubMed  CAS  Google Scholar 

  43. Fukuda T, Hashimoto H, Okayasu N, Kameyama A, Onogi H, Nakagawasai O, Nakazawa T, Kurosawa T, Hao Y, Isaji T, Tadano T, Narimatsu H, Taniguchi N, Gu J (2011) Alpha1,6-fucosyltransferase-deficient mice exhibit multiple behavioral abnormalities associated with a schizophrenia-like phenotype: importance of the balance between the dopamine and serotonin systems. J Biol Chem 286:18434–18443

    Article  PubMed  CAS  Google Scholar 

  44. Ohata S, Kinoshita S, Aoki R, Tanaka H, Wada H, Tsuruoka-Kinoshita S, Tsuboi T, Watabe S, Okamoto H (2009) Neuroepithelial cells require fucosylated glycans to guide the migration of vagus motor neuron progenitors in the developing zebrafish hindbrain. Development 136:1653–1663

    Article  PubMed  CAS  Google Scholar 

  45. Song Y, Willer JR, Scherer PC, Panzer JA, Kugath A, Skordalakes E, Gregg RG, Willer GB, Balice-Gordon RJ (2010) Neural and synaptic defects in slytherin, a zebrafish model for human congenital disorders of glycosylation. PLoS One 5:e13743

    Article  PubMed  Google Scholar 

  46. Murrey HE, Gama CI, Kalovidouris SA, Luo WI, Driggers EM, Porton B, Hsieh-Wilson LC (2006) Protein fucosylation regulates synapsin Ia/Ib expression and neuronal morphology in primary hippocampal neurons. Proc Natl Acad Sci U S A 103:21–26

    Article  PubMed  CAS  Google Scholar 

  47. Kudo T, Kaneko M, Iwasaki H, Togayachi A, Nishihara S, Abe K, Narimatsu H (2004) Normal embryonic and germ cell development in mice lacking alpha 1,3-fucosyltransferase IX (Fut9) which show disappearance of stage-specific embryonic antigen 1. Mol Cell Biol 24:4221–4228

    Article  PubMed  CAS  Google Scholar 

  48. Kudo T, Fujii T, Ikegami S, Inokuchi K, Takayama Y, Ikehara Y, Nishihara S, Togayachi A, Takahashi S, Tachibana K, Yuasa S, Narimatsu H (2006) Mice lacking alpha1,3-fucosyltransferase IX demonstrate disappearance of Lewis X structure in brain and increased anxiety-like behaviors. Glycobiology 17:1–9

    Article  PubMed  Google Scholar 

  49. Lühn K, Laskowska A, Pielage J, Klambt C, Ipe U, Vestweber D, Wild MK (2004) Identification and molecular cloning of a functional GDP-fucose transporter in Drosophila melanogaster. Exp Cell Res 301:242–250

    Article  PubMed  Google Scholar 

  50. Ishikawa HO, Higashi S, Ayukawa T, Sasamura T, Kitagawa M, Harigaya K, Aoki K, Ishida N, Sanai Y, Matsuno K (2005) Notch deficiency implicated in the pathogenesis of congenital disorder of glycosylation IIc. Proc Natl Acad Sci U S A 102:18532–18537

    Article  PubMed  CAS  Google Scholar 

  51. Robey EA, Bluestone JA (2004) Notch signaling in lymphocyte development and function. Curr Opin Immunol 16:360–366

    Article  PubMed  CAS  Google Scholar 

  52. Dallman MJ, Smith E, Benson RA, Lamb JR (2005) Notch: control of lymphocyte differentiation in the periphery. Curr Opin Immunol 17:259–266

    Article  PubMed  CAS  Google Scholar 

  53. Hirschberg CB (2001) Golgi nucleotide sugar transport and leukocyte adhesion deficiency II. J Clin Invest 108:3–6

    PubMed  CAS  Google Scholar 

  54. Puglielli L, Hirschberg CB (1999) Reconstitution, identification, and purification of the rat liver Golgi membrane GDP-fucose transporter. J Biol Chem 274:35596–35600

    Article  PubMed  CAS  Google Scholar 

  55. Gazit Y, Mory A, Etzioni A, Frydman M, Scheuerman O, Gershoni-Baruch R, Garty BZ (2010) Leukocyte adhesion deficiency type II: long-term follow-up and review of the literature. J Clin Immunol 30:308–313

    Article  PubMed  CAS  Google Scholar 

  56. Karsan A, Cornejo CJ, Winn RK, Schwartz BR, Way W, Lannir N, Gershoni-Baruch R, Etzioni A, Ochs HD, Harlan JM (1998) Leukocyte adhesion deficiency type II is a generalized defect of de novo GDP-fucose biosynthesis. Endothelial cell fucosylation is not required for neutrophil rolling on human nonlymphoid endothelium. J Clin Invest 101:2438–2445

    Article  PubMed  CAS  Google Scholar 

  57. Marquardt T, Lühn K, Srikrishna G, Freeze HH, Harms E, Vestweber D (1999) Correction of leukocyte adhesion deficiency type II with oral fucose. Blood 94:3976–3985

    PubMed  CAS  Google Scholar 

  58. Lühn K, Marquardt T, Harms E, Vestweber D (2001) Discontinuation of fucose therapy in LADII causes rapid loss of selectin ligands and rise of leukocyte counts. Blood 97:330–332

    Article  PubMed  Google Scholar 

  59. Sturla L, Puglielli L, Tonetti M, Berninsone P, Hirschberg CB, De Flora A, Etzioni A (2001) Impairment of the Golgi GDP-l-fucose transport and unresponsiveness to fucose replacement therapy in LAD II patients. Pediatr Res 49:537–542

    Article  PubMed  CAS  Google Scholar 

  60. Yakubenia S, Wild MK (2006) Leukocyte adhesion deficiency II. Advances and open questions. FEBS J 273:4390–4398

    Article  PubMed  CAS  Google Scholar 

  61. Ishikawa HO, Ayukawa T, Nakayama M, Higashi S, Kamiyama S, Nishihara S, Aoki K, Ishida N, Sanai Y, Matsuno K (2010) Two pathways for importing GDP-fucose into the endoplasmic reticulum lumen function redundantly in the O-fucosylation of Notch in Drosophila. J Biol Chem 285:4122–4129

    Article  PubMed  CAS  Google Scholar 

  62. Ashikov A, Routier F, Fuhlrott J, Helmus Y, Wild M, Gerardy-Schahn R, Bakker H (2005) The human solute carrier gene SLC35B4 encodes a bifunctional nucleotide sugar transporter with specificity for UDP-xylose and UDP-N-acetylglucosamine. J Biol Chem 280:27230–27235

    Article  PubMed  CAS  Google Scholar 

  63. Ishida N, Kawakita M (2004) Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35). Pflugers Arch 447:768–775

    Article  PubMed  CAS  Google Scholar 

  64. Chen W, Tang J, Stanley P (2005) Suppressors of alpha(1,3)fucosylation identified by expression cloning in the LEC11B gain-of-function CHO mutant. Glycobiology 15:259–269

    Article  PubMed  Google Scholar 

  65. Lu L, Hou X, Shi S, Korner C, Stanley P (2010) Slc35c2 promotes Notch1 fucosylation and is required for optimal Notch signaling in mammalian cells. J Biol Chem 285:36245–36254

    Article  PubMed  CAS  Google Scholar 

  66. Bengtson P, Larson C, Lundblad A, Larson G, Pahlsson P (2001) Identification of a missense mutation (G329A;Arg(110)→GLN) in the human FUT7 gene. J Biol Chem 276:31575–31582

    Article  PubMed  CAS  Google Scholar 

  67. Bengtson P, Lundblad A, Larson G, Pahlsson P (2002) Polymorphonuclear leukocytes from individuals carrying the G329A mutation in the alpha 1,3-fucosyltransferase VII gene (FUT7) roll on E- and P-selectins. J Immunol 169:3940–3946

    PubMed  CAS  Google Scholar 

  68. Handa K, Stroud MR, Hakomori S (1997) Sialosyl-fucosyl poly-LacNAc without the sialosyl-Lex epitope as the physiological myeloid cell ligand in E-selectin-dependent adhesion: studies under static and dynamic flow conditions. Biochemistry 36:12412–12420

    Article  PubMed  CAS  Google Scholar 

  69. Aakhus AM, Stavem P, Hovig T, Pedersen TM, Solum NO (1990) Studies on a patient with thrombocytopenia, giant platelets and a platelet membrane glycoprotein Ib with reduced amount of sialic acid. Br J Haematol 74:320–329

    Article  PubMed  CAS  Google Scholar 

  70. Gröttum KA, Solum NO (1969) Congenital thrombocytopenia with giant platelets: a defect in the platelet membrane. Br J Haematol 16:277–290

    Article  PubMed  Google Scholar 

  71. Kunishima S, Kamiya T, Saito H (2002) Genetic abnormalities of Bernard–Soulier syndrome. Int J Hematol 76:319–327

    Article  PubMed  CAS  Google Scholar 

  72. Willig TB, Breton-Gorius J, Elbim C, Mignotte V, Kaplan C, Mollicone R, Pasquier C, Filipe A, Mielot F, Cartron JP, Gougerot-Pocidalo MA, Debili N, Guichard J, Dommergues JP, Mohandas N, Tchernia G (2001) Macrothrombocytopenia with abnormal demarcation membranes in megakaryocytes and neutropenia with a complete lack of sialyl-Lewis-X antigen in leukocytes—a new syndrome? Blood 97:826–828

    Article  PubMed  CAS  Google Scholar 

  73. Martinez-Duncker I, Dupre T, Piller V, Piller F, Candelier JJ, Trichet C, Tchernia G, Oriol R, Mollicone R (2005) Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMP–sialic acid transporter. Blood 105:2671–2676

    Article  PubMed  CAS  Google Scholar 

  74. Jones C, Denecke J, Strater R, Stolting T, Schunicht Y, Zeuschner D, Klumperman J, Lefeber DJ, Spelten O, Zarbock A, Kelm S, Strenge K, Haslam SM, Lühn K, Stahl D, Gentile L, Schreiter T, Hilgard P, Beck-Sickinger AG, Marquardt T, Wild MK (2011) A novel type of macrothrombocytopenia associated with a defect in alpha2,3-sialylation. Am J Pathol 179:1969–1977

    Article  PubMed  CAS  Google Scholar 

  75. Hamada T, Mohle R, Hesselgesser J, Hoxie J, Nachman RL, Moore MA, Rafii S (1998) Transendothelial migration of megakaryocytes in response to stromal cell-derived factor 1 (SDF-1) enhances platelet formation. J Exp Med 188:539–548

    Article  PubMed  CAS  Google Scholar 

  76. Wopereis S, Grunewald S, Huijben KM, Morava E, Mollicone R, van Engelen BG, Lefeber DJ, Wevers RA (2007) Transferrin and apolipoprotein C-III isofocusing are complementary in the diagnosis of N- and O-glycan biosynthesis defects. Clin Chem 53:180–187

    Article  PubMed  CAS  Google Scholar 

  77. Crook M (1991) Sialic acid: its importance to platelet function in health and disease. Platelets 2:1–10

    Article  PubMed  CAS  Google Scholar 

  78. Gadhoum SZ, Sackstein R (2008) CD15 expression in human myeloid cell differentiation is regulated by sialidase activity. Nat Chem Biol 4:751–757

    Article  PubMed  CAS  Google Scholar 

  79. Greenberg J, Packham MA, Cazenave JP, Reimers HJ, Mustard JF (1975) Effects on platelet function of removal of platelet sialic acid by neuraminidase. Lab Invest 32:476–484

    PubMed  CAS  Google Scholar 

  80. Grewal PK, Uchiyama S, Ditto D, Varki N, Le DT, Nizet V, Marth JD (2008) The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med 14:648–655

    Article  PubMed  CAS  Google Scholar 

  81. Sorensen AL, Rumjantseva V, Nayeb-Hashemi S, Clausen H, Hartwig JH, Wandall HH, Hoffmeister KM (2009) Role of sialic acid for platelet life span: exposure of beta-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes. Blood 114:1645–1654

    Article  PubMed  Google Scholar 

  82. Kayser H, Zeitler R, Kannicht C, Grunow D, Nuck R, Reutter W (1992) Biosynthesis of a nonphysiological sialic acid in different rat organs, using N-propanoyl-d-hexosamines as precursors. J Biol Chem 267:16934–16938

    PubMed  CAS  Google Scholar 

  83. Gu X, Wang DI (1998) Improvement of interferon-gamma sialylation in Chinese hamster ovary cell culture by feeding of N-acetylmannosamine. Biotechnol Bioeng 58:642–648

    Article  PubMed  CAS  Google Scholar 

  84. Petri B, Broermann A, Li H, Khandoga AG, Zarbock A, Krombach F, Goerge T, Schneider SW, Jones C, Nieswandt B, Wild MK, Vestweber D (2010) von Willebrand factor promotes leukocyte extravasation. Blood 116:4712–4719

    Article  PubMed  CAS  Google Scholar 

  85. Wild MK, Lühn K, Marquardt T, Vestweber D (2002) Leukocyte adhesion deficiency II: therapy and genetic defect. Cells Tissues Organs 172:161–173

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We would like to thank the patients and their parents for their patience with us, for providing blood samples and for their permission to publish the data.

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  1. Weatherall Institute of Molecular Medicine, MRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK

    Kerstin Lühn

  2. Max Planck Institute for Molecular Biomedicine, Röntgenstr. 20, 48149, Münster, Germany

    Martin K. Wild

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  1. Kerstin Lühn
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Correspondence to Martin K. Wild.

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This article is published as part of the Special Issue on Glycosylation and Immunity [34:3].

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Lühn, K., Wild, M.K. Human deficiencies of fucosylation and sialylation affecting selectin ligands. Semin Immunopathol 34, 383–399 (2012). https://doi.org/10.1007/s00281-012-0304-1

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